Protocol Title: Phase 2 trial of Gamunex (Intravenous Gamma globulin) for Sickle Cell Acute Pain Principal Investigator: Deepa Manwani Co-Investigators: Paul S. Frenette, Patricia A. Shi, Hillel Cohen, Catherine Driscoll, Veronica Carullo ABSTRACT Sickle cell anemia is one of the most common hematologic diseases in the world. The most common clinical manifestation of this disease is the recurrence of vaso-occlusive episodes (?crises?) for which there is currently no therapy other than supportive care and analgesics. Studies using a mouse model of sickle cell disease (SCD) suggest that leukocytes (WBCs) that are adherent to the vessel wall of post-capillary and collecting venules play a key role in vascular occlusion by interacting with sickle eythrocytes (RBCs)1-3. In search for the molecular mechanisms responsible for these interactions, it was found that intravenous immune globulin (IVIG) had a profound effect on the interactions among RBCs, WBCs, and the endothelium, improved blood flow in venules of the cremaster muscle and, most importantly, impacted on the overall survival of sickle cell mice.4,5 A pilot phase I double blind placebo controlled randomized, dose escalation study demonstrated that while doses up to 800mg/kg can be safely administered to sickle cell disease patients during acute pain events, a 400mg/kg dose provided optimal biomarker and clinical efficacy with decreased infusion associated adverse events. We therefore want to evaluate intravenous immune globulin (IVIG) at the 400mg/kg dose in a phase II clinical study in sickle cell disease patients that are admitted to Montefiore Medical Center for vaso-occlusive crisis (VOC). Hypothesis: 1) IVIG at 400mg/kg is well tolerated by patients with sickle cell disease admitted with VOC. 2) IVIG can be effective in ameliorating VOC in patients with sickle cell disease. Specific Aims: 1) To evaluate the effect of a single dose of 400mg/kg of IV Gamunex on time to resolution of VOC in subjects 8-21years of age hospitalized for sickle cell VOC in a randomized, double blind placebo controlled Phase 2 trial. 2) To further evaluate safety of a single dose of 400mg/kg of IV Gamunex in subjects 8-21years of age hospitalized for sickle cell VOC 3) To evaluate biomarkers of adhesion and inflammation and secondary clinical end points (e.g. total opioid use, length of hospitalization and change in LDH) in subjects enrolled on this study).